SUMMARY Modern antiretroviral therapy has brought about significantly increased life expectancies for persons living with HIV/AIDS (PLWH). However, the effort to reduce the occurrence of cardiovascular disease and various malignancies in this population remains an important public health priority. Arguably, the most effective way to prevent these diseases in PLWH would be to reduce the prevalence of cigarette smoking. Despite the significant need, relatively few smoking cessation trials with PLWH appear in the literature. Thus, efforts to develop and evaluate sustainable, low cost evidence-based cessation interventions for smokers with HIV are needed. Given the widespread proliferation of mobile phones, the potential of using mHealth applications to improve the reach and efficacy of cessation interventions is promising, but evidence of efficacy is lacking, particularly among PLWH. With these needs in mind, the overarching purpose of the proposed project is to evaluate a fully automated smartphone intervention for HIV+ smokers. Participants (n=500) will be randomized to one of two treatment conditions: 1) Standard Treatment (ST, n=250) or Automated Video-Assisted Smoking Treatment (AVAST, n=250). ST participants will be electronically connected to state quitline- delivered cessation treatment, consisting of proactive phone counseling plus nicotine replacement therapy (NRT) in the form of transdermal patches. This approach, frequently referred to as Ask Advise Connect (AAC), was developed by our team and has been successfully implemented in numerous health systems. ST will be compared to AVAST, a fully automated treatment delivery approach. In the AVAST condition, participants will receive NRT plus an interactive smartphone-based intervention that comprises individually tailored audio/video and text content. Foundational programming and developmental work for AVAST has already been completed by the Stephenson Cancer Center's mHealth Shared Resource, and results from a series of pilot studies (including extensive work conducted at both proposed HIV clinic recruitment sites) with beta versions of the mobile application and data management system are extremely encouraging. The major goal of this project is to determine if AVAST performs better, in terms of facilitating long-term smoking abstinence (i.e., biochemically verified abstinence 12 months post-enrollment), than the more resource-intensive ST approach. If efficacy is established, the AVAST approach will be readily adoptable by various HIV clinic and community-based organizations, and offer an efficient way to allocate limited public health resources to tobacco control interventions. The primary aim is to evaluate the efficacy of AVAST for facilitating smoking cessation among PLWH. Secondary aims include: 1) exploring potential mediators and moderators, and 2) conducting economic evaluations to assess the cost and cost-effectiveness of AVAST. In sum, there is a critical need for efficacious, cost-effective, and sustainable cessation treatments for PLWH who smoke tobacco. The proposed AVAST intervention has been designed to help fill this need.